Case Report
Otolaryngology–
Transcervical Ultrasound Identifies
Primary Tumor Site of Unknown
Primary Head and Neck Squamous
Cell Carcinoma
Wojciech K. Mydlarz, MD1, Jia Liu, MD1, Ray Blanco, MD1,2, and
Carole Fakhry, MD, MPH1,2,3
No sponsorships or competing interests have been disclosed for this article.
Keywords
human papillomavirus, unknown primary, oropharyngeal
cancer, ultrasound, head and neck squamous cell carcinoma
Received June 10, 2014; revised July 16, 2014; accepted August 7,
2014.
H
ead and neck squamous cell carcinomas (HNSCCs)
of unknown primary site (UP) account for approxi-
mately 4% of HNSCCs.1 These cases have histori-
cally been subclinical tumors arising from the nasopharynx,
hypopharynx, or oropharynx. In the era of human papillo-
mavirus (HPV)–positive HNSCCs, the presence of HPV in
cervical malignancy of UP has been strongly associated
with oropharyngeal primary tumors.2 Tumors that are HPV–
positive are typically small and arise from cryptic lingual
and palatine lymphoid tissues, rendering primary tumor
detection challenging.3 The traditional diagnostic paradigm
for finding the primary tumor consists of a physical exami-
nation, fiber-optic laryngoscopy, and imaging. If these tech-
niques are unsuccessful, operative examination under
anesthesia is warranted, including direct laryngoscopy with
‘‘blind’’ biopsies directed at the nasopharynx, hypopharynx,
oropharynx, larynx, and palatine and lingual tonsillectomy.
Failure to identify the primary tumor site subsequently
necessitates radiation of Waldeyer’s ring and concurrent
chemotherapy. This report shows that transcervical ultra-
sound (US) can be used to localize oropharyngeal tumors.
The study was reviewed and approved by the Greater
Baltimore Medical Center Institutional Review Board.
Case Report
A 60-year-old white man, a former smoker and occasional
drinker, presented with a 1-month history of enlarging left
neck mass. By report, there was no evidence of a primary
site clinically. Fine-needle aspiration (FNA) of the neck
mass revealed nonkeratinizing squamous cell carcinoma.
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Head and Neck Surgery
2014, Vol. 151(6) 1090–1092
Ó American Academy of
Otolaryngology—Head and Neck
Surgery Foundation 2014
Reprints and permission:
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DOI: 10.1177/0194599814549181
http://otojournal.org
Examination under anesthesia with direct laryngoscopy with
biopsies of the base of tongue (BOT), nasopharynx, and
bilateral palatine tonsillectomies failed to reveal the primary
site.
The patient presented to our clinic for secondary evalua-
tion with a 2-cm left level II cervical lymph node. There
was no evidence of a primary tumor on physical or fiber-
optic examinations. Review of the FNA confirmed the cyto-
logic diagnosis of p16-positive squamous cell carcinoma.
Positron emission tomography/computed tomography (PET/
CT) revealed small foci of uptake without CT abnormality
in the right nasopharynx (standardized uptake value [SUV]
5.6) and retropharynx (SUV 4.3) and 2 enlarged left level II
lymph nodes measuring 1.7 3 2.3 cm and 1.2 3 0.7 cm
with SUVs of 7.5 and 4.1, respectively (Figure 1).
A transcervical US was performed, demonstrating a
hypoechoic heterogeneous lesion deep in the left BOT
approaching the vallecula (Figure 2). The 1.2-cm (superior-
inferior), 1.2-cm (anterior-posterior), and 1.3-cm (medial-lat-
eral) mass was ill defined and purely endophytic. On parasa-
gittal view, the lesion appeared to be approximately 9.2 mm
from the mucosal surface of the BOT apex and 3.5 mm from
the mucosal surface of the vallecula.
Direct laryngoscopy was again inconclusive. Directed deep
biopsies based on the preoperative US revealed at least squa-
mous cell carcinoma in situ. The patient was treated with cis-
platin, concurrent with standard fractionation external beam
radiation. Posttreatment PET/CT revealed no evidence of dis-
ease, and the patient is free of disease at 2 years.
1
Department of Otolaryngology–Head and Neck Surgery, Johns Hopkins
Medicine, Baltimore, Maryland, USA
2
Milton J. Dance Jr Head and Neck Cancer Center, Greater Baltimore
Medical Center, Baltimore, Maryland, USA
3
Department of Epidemiology, Johns Hopkins Bloomberg School of Public
Health, Baltimore, Maryland, USA
Corresponding Author:
Carole Fakhry, MD, MPH, Department of Otolaryngology–Head and Neck
Surgery, Johns Hopkins Medicine, 601 N Caroline Street, 6th Floor,
Baltimore, MD 21287-0910, USA.
Email: cfakhry@jhmi.edu
Mydlarz et al
Figure 1. Positron emission tomography/computed tomography
(CT) findings. Hypermetabolic focus in the right nasopharynx (A)
and hypopharynx (C). (B, D) CT without corresponding abnormal-
ities. (E, F) Enlarged cervical nodes in left level II.
Discussion
This case demonstrates the successful application of preo-
perative transcervical US to visualize a BOT malignancy
and to help direct biopsies in a patient who would other-
wise have been treated as having HNSCC of UP.
Ultrasonography is low risk, inexpensive, and repeatable,
and it can be performed easily in an office setting.
Alternative approaches for this patient would be to per-
form lingual tonsillectomy for diagnostic purposes or to
treat the entire pharyngeal axis with radiation for UP.1
Lingual tonsillectomy has inherent risks of anesthesia,
bleeding, dysphagia, pain, and delay in definitive radio-
therapy. In this case, it is also possible that a lingual ton-
sillectomy may not have detected this deep-seated tumor.
The UP tumor treatment includes the entire pharyngeal
axis and unnecessarily exposes the constrictor muscles
and mucosa to radiation, thereby increasing the risk of
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1091
Figure 2. Transcervical ultrasound of the tongue base. A slightly
hypoechoic heterogeneous lesion was found within the deep
tongue base. (A) Coronal view (30° from hyoid, B).
acute and chronic side effects while also underdosing a
potentially targetable and curable cancer.
In this case, US enabled identification of the primary
lesion when PET/CT failed to reveal any abnormality in the
oropharynx. Similarly, there was no asymmetry or mass on
CT. Instead, the US revealed a small endophytic lesion deep
in the tongue base without any clinically appreciable overly-
ing mucosal changes or palpable abnormality. Indeed, this
BOT lesion was identified despite previously performed
blind biopsies. Ultrasound-guided transcervical FNA biopsy
of the tongue base is feasible,4 and the use of US to search
for the primary site of UP HNSCC has been previously
reported.5 Oropharyngeal US may have utility in the evalua-
tion of UP and oropharyngeal HNSCCs, but further investi-
gation is necessary.
Author Contributions
Wojciech K. Mydlarz, acquisition, analysis and interpretation of
data, revising, final approval; Jia Liu, acquisition, analysis and
interpretation of data, final approval; Ray Blanco, data analysis,
manuscript revision, final approval; Carole Fakhry, acquisition,
analysis, manuscript conception, design, drafting, revising, final
approval.
1092 Otolaryngology–Head and Neck Surgery 151(6)

Disclosures papillomavirus type 16-negative head and neck cancers. J Natl

Competing interests: None.
Sponsorships: None.
Funding source: None.
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